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Open Access Research article

The role of LDH serum levels in predicting global outcome in HCC patients treated with sorafenib: implications for clinical management

Luca Faloppi1, Mario Scartozzi1*, Maristella Bianconi1, Gianluca Svegliati Baroni2, Pierluigi Toniutto3, Riccardo Giampieri1, Michela Del Prete1, Samuele De Minicis2, Davide Bitetto3, Cristian Loretelli4, Marco D’Anzeo1, Antonio Benedetti2 and Stefano Cascinu1

Author Affiliations

1 Department of Medical Oncology, Translational Oncology Unit, AOU Ospedali Riuniti, Università Politecnica delle Marche, Via Conca 71, 60126 Ancona, Italy

2 Clinica di Gastroenterologia, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy

3 Internal Medicine, Department of Medical Sciences Clinical and Experimental, University of Udine, Udine, Italy

4 Cancer Genetics Program, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA

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BMC Cancer 2014, 14:110  doi:10.1186/1471-2407-14-110

Published: 20 February 2014

Abstract

Background

In many tumour types serumlactate dehydrogenase (LDH) levels proved to represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis. As we previously reported LDH is an important predictive factor in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). Sorafenib represents the therapeutic stronghold in advanced HCC patients. As a tyrosine kinase inhibitor (TKI) mainly directed against the angiogenetic pathway, the correlation of sorafenib administration with markers of hypoxia could be an important tool in patients management. Aim of our analysis was to evaluate the role of LDH pre-treatment levels and its variation during treatment in HCC patients receiving sorafenib.

Methods

78 patients were available for our analysis. For all patients LDH values were collected within one month before the start of treatment and after the end of therapy. For study purposes we divided our patients into two groups, according to LDH pre-treatment levels, cut-off levels was determined with ROC curve analysis. Patients were, also, classified according to the variation in LDH serum levels pre- and post-treatment (increased vs decreased).

Results

Patients proved homogeneous for all clinical characteristics analyzed. In patients with LDH values under the cut-off median progression free survival (PFS) was 6.7 months, whereas it was 1.9 months in patients above the cut-off (p = 0.0002). Accordingly median overall survival (OS) was 13.2 months and 4.9 months (p = 0.0006). In patients with decreased LDH values after treatment median PFS was 6.8 months, and median OS was 21.0 months, whereas PFS was 2.9 months and OS 8.6 months in patients with increased LDH levels (PFS: p = 0.0087; OS: p = 0.0035).

Conclusions

In our experience, LDH seemed able to predict clinical outcome in terms of PFS and OS for HCC patients treated with sorafenib. Given the correlation between LDH levels and tumour angiogenesis we can speculate that patients with high LDH pretreatment levels may be optimal candidates for other emerging therapeutic agents or strategies targeting different molecular pathways.

Keywords:
Hepatocellular carcinoma; Lactate dehydrogenase; Sorafenib; Angiogenesis